Identification Of LncRNAs In The Spinal Cord Of A Lumbar Disc Herniation Rat Model

Background: Radicular pain,which can be caused by a lesion or autologous nucleus pulposus(NP)implantation,is associated with gene expression changes in the pain signalling pathway.Long noncoding RNAs(lnc RNAs)have been recently shown to play critical roles in neuropathic pain.However,little is known about the mechanistic role of lnc RNAs in lumbar disc herniation(LDH).Identifying lnc RNA expression patterns in the spinal cord under normal and NP-implantation conditions is essential for understanding the genetic mechanisms of neuropathic pain.The results: Lumbar disc herniation(LDH)induced rapid and persistent pain hypersensitivity,which was characterized by mechanical allodynia and heat hyperalgesia.Meanwhile,the lnc RNA microarray and m RNA microarray analyses showed that the expression profiles of lnc RNAs and m RNAs between the LDH and sham groups were markedly changed at 7 days post operation.A total of 19 differentially expressed(>1.5-fold)lnc RNAs(13 up-regulated,6 down-regulated)and 103 m RNAs(40 up-regulated,63 down-regulated)were identified.The expression patterns of several lnc RNAs and m RNAs were further confirmed by q PCR.Functional analysis of the differentially expressed m RNAs showed that the most significant enriched biological processes of the up-regulated genes in LDH included chemotaxis,immune response,and positive regulation of inflammatory response,which are important pathogenic mechanisms underlying neuropathic pain.These 19 differentially expressed lnc RNAs have overlapping m RNAs in the genome,which are related to Glutamatergic synapse,Cytokine-cytokine receptor interaction,and the TGF-beta signalling pathway.Conclusion: Our findings revealed the expression pattern of lnc RNAs and m RNAs in the rat spinal cord under neuropathic pain conditions.These lnc RNAs and m RNAs may represent new therapeutic targets for the treatment of radicular pain.In addition,The study shows that the lumbar disc herniation causes the activation of microglia in the spinal cord,and then lead to the expression of lnc RNA-14238,promote the expression of TLR-4,and finnally influence the expression of NF-kappa B and the activation of the active substance of the downstream CBS receptor.Stimulating the excitatory and postsynaptic currents of neurons in the dorsal horn of the spinal cord,resulting in LDH central sensitization,and eventually the central sensitization of the LDH.This will provide a new target for clinical treatment of lumbar disc pain.